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| United States Patent |
5,015,452
|
|
Matijevic
|
May 14, 1991
|
Process for synthesis of uniform colloidal particles of rare earth oxides
Abstract
An improved process for the preparation of monodispersed spherical
colloidal particles from rare earth salts is disclosed. These colloidal
particles are obtained in this process by homogeneous precipitation
techniques involving the forced hydrolysis of rare earth salts in aqueous
media. More specifically, this process initially involves the formation of
hydrolyzed cations which are precursors or intermediate to precipitation
of the desired colloidal particle. The objective in the formation of this
precursor species is to reach critical supersaturation concentration of
this particle forming species so that only one burst of nuclei occurs.
Colloidal particle formation is then effected by diffusion of solutes onto
the existing nuclei. The improvements of this process reside, in part, in
the ability to control the kinetics of formation of this intermediate
species. Such control permits the formation of colloidal dispersions
having very narrow particle size distribution. The colloidal dispersions
of these particles are also quite stable. The rare earth colloidal
particles prepared by this process are useful in both industrial and
biologic environments.
| Inventors:
|
Matijevic; Egon (Potsdam, NY)
|
| Assignee:
|
Clarkson University (Potsdam, NY)
|
| Appl. No.:
|
003900 |
| Filed:
|
January 16, 1987 |
| Current U.S. Class: |
423/263; 252/301.36; 252/301.4R; 423/21.1 |
| Intern'l Class: |
C01F 017/00 |
| Field of Search: |
423/263,21.1,592
252/301.4 R,301.36
210/912
501/152
|
References Cited
U.S. Patent Documents
| 3669897 | Jun., 1972 | Wachtel | 423/263.
|
| 4010242 | Mar., 1977 | Iler et al. | 423/592.
|
| 4263164 | Apr., 1981 | Swinkels et al. | 423/263.
|
| 4529410 | Jul., 1985 | Khabdji et al. | 423/263.
|
| Foreign Patent Documents |
| 0167426 | Oct., 1983 | JP | 423/263.
|
| 0013625 | Jan., 1984 | JP | 423/263.
|
| 1000532 | Jan., 1986 | JP | 423/263.
|
Other References
"Aluminum Hydrous Oxide Sols", Catone et al., Journal of Colloid and
Interface Science, vol. 48, No. 2, Aug. 8, 1974, pp. 291-301.
Monodispersed Metal(hydrous)Oxides-Matijevie, American Chemical Society,
1981, 14, 22-29.
Matijevic, E., "Monodispersed Colloids: Art and Science", 1986, pp. 12-20.
Kirk-Othmer, "Rare Earth Elements", 1986, pp. 150-167.
Matijevic, E., "Production of Monodispersed Colloidal Particles", 1985, pp.
483-516.
|
Primary Examiner: Stoll; Robert L.
Assistant Examiner: Harvey; Paige C.
Attorney, Agent or Firm: Oblon, Fisher, Spivak, McClelland & Maier
Goverment Interests
GOVERNMENT CONTRACT
The inventions described and claimed herein were made under a grant from
the U.S. Air Force Office of Scientific Research (AFOSR Contract
F49620-85-C-0142) and the United States Government has rights in such
inventions.
Parent Case Text
CROSS REFERENCE TO RELATED APPLICATION
This application is a continuation-in part of U.S. application Ser. No.
931,352, filed Nov. 17, 1986, entitled Process for Synthesis of Uniform
Colloidal Particles of Rare Earth Oxides, now abandoned.
Claims
What is claimed is:
1. In a process for the preparation of colloidal particles from rare earth
salts by homogeneous precipitation techniques involving the forced
hydrolysis of a hydrated cation at elevated temperatures, the improvement
comprising:
(a) providing an aqueous solution, at an initial pH in the range of from
about 4.5 to about 6, containing one or more hydrated rare earth cations;
(b) heating the aqueous solution containing one or more hydrated rare earth
cations to a temperature in the range of from about 70.degree. to about
90.degree. C., so as to effect deprotonation of the hydrated rare earth
cations under conditions conducive to control over the kinetics of
formation of a precursor of the colloidal particles, and thereby generate
in single burst of nuclei preliminary to formation of colloidal particles;
(c) aging the solution, in step (b) the extent of such aging being based
upon the growth of said nuclei to the desired particle size for the
colloidal particles; and
(d) separating the colloidal particles from the solution in step (c) upon
attainment of the particles of the desired particle size.
2. The process of claim 1, wherein the source of rare earth cation is a
salt which is selected from the group consisting of gadolinium, terbium
and europium salts.
3. The process of claim 1, wherein the solution in step (b) contains a base
as a source of hydroxide ions.
4. The process of claim 3, wherein the source of hydroxide ions is an
organic base, said organic base thermally decomposing in said aqueous
solution, at temperatures in the range of from about 70.degree. to about
90.degree. C., to produce a deprotonation accelerator effective amount of
hydroxide ions.
5. The process of claim 4, wherein the precursor to colloidal particle
formation is generated in solution at supersaturation concentrations and
under conditions so that only a single burst of particle forming nuclei
occurs.
6. The process of claim 4, wherein the aqueous solution containing one or
more hydrated rare earth cations is acidified so as to increase the size
of colloidal particle without extended aging, the acid conscentration of
said solution being, at all times, maintained below about
1.times.10.sup.-2 mol dm.sup.-3.
7. The process of claim 1, wherein the concentration of rare earth salt in
solution is in the range from about 1.times.10.sup.-3 mol dm.sup.-3 to
about 2.times.10.sup.31 2 mol dm.sup.-3.
8. The process of claim 3, wherein the colloidal particles are heated under
conditions conducive to decomposition of organic matter, while preserving
the colloidal characteristic of said particles.
9. The process of claim 1, wherein said rare earth salts used are rare
earth nitrates and halides.
Description
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a process and to a composition of matter
resulting from this process. More specifically, this invention is directed
to processes for the preparation of spherical colloidal particles of rare
earth (hydrous) oxides. The particles produced in accordance with these
processes have a very narrow particles size distribution and well defined
morphology. These particles have advantageous optical properties (i.e.
fluorescence) and are, thus, useful in diagnostic applications in the
optical separation of various constituents of complex fluids (i.e. blood,
cerebrospinal fluid or urine).
2. Description of the Prior Art
The preparation of colloidal particles from organic substances has, until
very recently, been a highly empirical "science". For the most part, the
efficacy of such processes was quite subjective and generally the relative
success or failure thereof required laborious trial and error in order to
attain adequate process definition. More specifically, the efficacy of a
particular technique, even if it were reproducible to a degree, rarely
produced a consistently acceptable product. The inability to achieve
reproducible results from such processes has, thus, led many to regard the
synthesis of inorganic colloidal particles as largely the domain of the
empiricist.
With the advent of more sophisticated analytical tools (i.e. electron
microscopy), the fascination with inorganic colloidal particles, and more
particularly, monodispersed inorganic colloidal particles, has been
rekindled. The initial interest in such materials was primarily as a
scientific curiosity, however, more recent developments have found them
useful as supports for catalysts, in ceramics, pigments, films, recording
media, coatings, in various diagnostic and therapeutic environments, as
well as a myriad of other applications.
The term "monodispersed" as used in the discussion of the prior art and
throughout the balance of this disclosure is intended as referring to a
population of particulate materials having a narrow particles size
distribution.
A survey of the various techniques for synthesis of monodispersed,
inorganic colloidal particles has recently appeared in the technical
literature, see Matijevic, E., "Monodispersed Colloids: Art and Science",
Langmuir, Vol. 2, No. 1, pp. 12-20 (1986).
The procedures which have been developed by the inventor for synthesis of
inorganic colloidal dispersions of narrow particle size distribution have
been described in detail in a number of papers which have also appeared in
the technical literature, see for example, Matijevic, E., Annu. Rev.
Mater. Sci. (1985), 15, 483 and Matijevic, E., Acc. Chem. Res. (1981), 14,
22. Two of the procedures described in the above articles can be
conveniently grouped into the following categories: (1) precipitation from
homogeneous solution (i.e. forced hydrolysis, controlled release of anions
and controlled release of cations); and (2) phase transformations. What
is, however, to be appreciated is that each of the above procedures will
have one or more shortcomings or advantages for synthesis of a specific
colloidal material. Thus, the production of an acceptable product in
accordance with each of the processes from the same starting materials is
highly unpredictable. More specifically, in order to produce colloidal
particles of specific characteristics, both of the above procedures may
have to be attempted before one can be identified as potentially useful or
efficacious. At that point, additional refinement will be required before
an acceptable product is attainable.
In the procedures involving precipitation of inorganic compounds from
homogeneous solutions, the precursors to the formation of the solid phase
are, in most instances, one or more solute complexes. This procedure is,
thus, based upon the control of kinetics of the complexation reaction in
order to achieve a single burst of nuclei, which are then allowed to grow
uniformly, resulting in particles of narrow size distribution. Where the
constituent solutes are generated at the proper rate, their even
distribution onto existing nuclei results in the least increase in total
free energy of the dispersion, thus, controlling the growth of such
particles by proper control of particle charge. Control of the charge in
such particles is traditionally achieved by adjustment in pH or through
the introduction of additives. In the absence of such control in charge,
aggregation of such particles will result.
The phrase "forced hydrolysis" is used hereinafter to reference the process
or ability of many hydrated metal ions (especially polyvalent metal
cations) to readily deprotonate in aqueous solution at elevated
temperatures. This characteristic can be used to advantage in the
preparation of colloidal particles from such materials. Since the
hydrolyzed species of these metal ions are intermediates to precipitation
of the corresponding hydroxides, it is possible to generate uniform
particles simply by heating metal salt solutions. In this forced
hydrolysis procedure, the pH and the nature of the anions play a dominant
role. In some instances, anions may simply affect particle morphology
without being integrated within the solid phase, or can be incorporated
within the solid phase as impurities into either an amorphous or
crystalline solid. Lastly, these anions can through stoichiometric
compounds, as in the case of alunites.
Because of the nature of the colloidal particles, and the various methods
used in their preparation, their physical properties are often
unpredictable. More specifically, the preparation of colloidal particles
from rare earth oxides by traditional methods did not permit the
attainment of particles of predictable morpology or uniform size.
The traditional procedures for the synthesis of rare earth oxides are both
diverse and energy intensive (Kirk and Othmer, Encyclopedia of Chemical
Technology, (2nd Ed), Vol. 17, 163). The so-called "dry" approach to such
synthesis involves the initial formation of salts (i.e., hydroxide,
carbonate, oxalate, nitrate, sulfate, etc.). These salts can be converted
to the corresponding oxide by standard calcination techniques (at
temperatures in excess of 850.degree. C.). These salts are, thus,
decomposed to the corresponding oxides which are essentially insoluble in
aqueous media.
The rare earth oxides produced in the above manner have had rather limited
applications, and then primarily in industrial environments. Rare earth
compounds, including rare earth oxides, have been mainly used in glass
manufacturing and polishing, arc carbons, catalysts, lighter flints, and
in ceramic applications.
The adaptation of colloidal materials to biological environment introduces
a unique set of variables. For examples, if a colloidal material is to be
used in a fluid environment, its ability to form stable dispersions can be
critical. In the event the colloidal material is to be used as an
indicator or a label, the photo-optical or magnetic properties may be of
paramount importance. Colloidal particles are attractive for biological
applications because they are relatively inert and can be produced in
quantity from readily available materials at relatively low cost.
Unfortunately, the inability to prepare such materials in a reproducible
manner, with predictable properties, has hindered their general
acceptance. Accordingly, there is a continuing need to provide a cost
efficient reproducible process for the synthesis of inert, inorganic
colloidal particles.
OBJECTS OF THE INVENTION
It is the principle object of this invention to remedy the above as well as
related deficiencies in the prior art.
It is another object of this invention to provide a reproducible energy
efficient process for the synthesis of monodispersed rare earth (hydrous)
oxide particles.
It is yet another object of this invention to provide a reproducible,
energy efficient process for the synthesis of colloidal particles of rare
earth (hydrous) oxides by an improved forced hydrolysis process.
It is still yet another object of this invention to provide a reproducible,
energy efficient, process for the synthesis of a class of rare earth
(hydrous) oxides which can be useful in the identification of constituents
of complex fluids, notably, biological fluids.
It is a further object of this invention to provide a reproducible, energy
efficient process for the synthesis of a class of rare earth (hydrous)
oxides whose fluorescent properties can be tailored to the optical
separation and identification of constituents of biological fluids.
It is yet a further object of this invention to provide a reproducible,
energy efficient process for the synthesis of rare earth (hydrous) oxides
which can form stable dispersions in aqueous media.
It is still yet a further object of this invention to provide a
reproducible, energy efficient process for the synthesis of rare earth
(hydrous) oxides of gadolinium, terbium and europium.
SUMMARY OF THE INVENTION
The above and related objects are achieved by providing a process for the
preparation of colloidal dispersions of rare earth (hydrous) oxides from
their corresponding salts. The particles produced by this process have
well defined morphological properties and are of essentially uniform
particle size. This process involves the forced hydrolysis of such salts
in aqueous solution under conditions which initially results in the
formation of an intermediate or precursor species. The forced hydrolysis
of the rare earth salts in accordance with this process is achieved by
heating solutions of these salts under deprotonation conditions; most
preferably, in the presence of a compound which affords for controlled
release of hydroxide ions, i.e. an organic compound such as urea. The
deprotonation conditions of this invention permit precise control of the
kinetics of formation of a precursor species which are intermediates in
the formation nuclei of the desired colloidal particle. The conditions and
relative concentration of reactants involved in the formation of the
individual precursor species for a specific rare earth colloid will,
however, vary somewhat from material, and the stability in formation of
each such precursor must be established by experimentation.
In the preferred embodiments of the process of this invention, such forced
hydrolysis is effected in aqueous media and in the presence of a source of
hydroxide ions (i.e. organic base). This preferred embodiment of the
process of this invention is also conservative of energy and can be
performed with standard equipment under relatively mild operating
conditions. The intermediate or precursor is formed under conditions, and
in sufficient concentration, to supersaturate the reaction medium. At or
slightly above this point of supersaturation, a single burst of nuclei
occurs, thus, initiating growth. Particle growth then proceeds by
diffusion of solute from the medium onto the existing nuclei.
The particles recovered from the fluid medium comprise the hydroxycarbonate
of the corresponding rare earth salt. The hydroxycarbonate particles can
be readily converted to the corresponding oxide by thermal decomposition.
This decomposition of the hydroxycarbonate to the oxide does not
materially alter the morphology or photo-optical properties of these
particles.
The rare earth (hydrous) oxides obtained by this process will vary in
physical characteristics and crystallinity, depending upon their chemical
composition. The preferred gadolinium oxides of this invention are, for
example, generally spherical in shape. These oxides are fluorescent and
can be used in biological environments as indicators.
BRIEF DESCRIPTION OF THE DRAWINGS
FIGS. 1a and 1b are pen and ink reproductions of transmission electron
micrographs of the gandolinium hydroxycarbonate particles of Example 1a
and 1b respectively.
FIG. 2 is a fluorescence emission spectrum of the gadolinium
hydroxycarbonate of Example 1 at 436 nm excitation wavelength.
FIG. 3 is a pen and ink reproduction of a transmission electron micrograph
of the terbium hydroxycarbonate of Example 2.
FIG. 4 is a pen and ink reproduction of a transmission electron micrograph
of the europium hydroxycarbonate of Example 3.
FIG. 5 is a graphical illustration of the electrokinetic measurement of
gadolinium and terbium hydroxycarbonates prepared in accordance with
procedures of Examples 1 and 2 respectively.
FIG. 6 illustrates an adaptation of this invention to a continuous flow
process for the synthesis of colloidal particles from rare earth salts.
DESCRIPTION OF THE INVENTION INCLUDING PREFERRED EMBODIMENTS
This invention provides a reproducible process for the synthesis of
spherical colloidal particles having narrow particle size distribution
from rare earth salts (e.g. gadolinium, terbium and europium). These
colloidal particles are obtained by homogeneous precipitation techniques
involving the forced hydrolysis of rare earth slats in aqueous media. The
conditions prevailing in this process are designed to insure control in
the kinetics of formation of the species which are precursors to particle
growth. This process permits the growth of colloidal particles from such
salts in a controlled manner, thus, insuring narrow particle size
distribution.
Preliminary to further discussion of this process, it would be helpful to
briefly define some of the terms and phrases used throughout this
description and in the appended claims.
The phrase "colloidal particles" is intended, in the context of this
invention, as inclusive of the hydroxycarbonates and oxides of rare earths
having a particle size of less than one (1) micron. It is also understood
to be inclusive of colloidal particle mixtures of hydroxycarbonates and
oxides of rare earths.
The phrase "rare earth" is intended as descriptive of the lanthanide series
of elements of the periodic table having an atomic number of from 57 to
71. This phrase, thus, contemplates the following elements:
Lanthanum (La)
Cerium (Ce)
Praseodymium (Pr)
Neodymium (Nd)
Promethium (Pm)
Samarium (Sm)
Europium (Eu)
Gadolinium (Gd)
Terbium (Tb)
Dysprosium (Dy)
Holmium (Ho)
Erbium (Er)
Thulium (Tm)
Ytterbium (Yb)
Lutetium (Lu)
The salts of the rare earths which are preferred for use in this process
include the halide and nitrate salts.
These rare earth salts are readily soluble and can be dissolved in aqueous
medium (preferably water). The concentration of these salts in such
solutions is precisely adjusted within the following limits:
1.times.10.sup.-3 mol dm.sup.-3 to 2.times.10.sup.-2 mol dm.sup.-3. Once
these salts (polyvalent cations) dissolve in aqueous media, they readily
hydrolyze. In the preferred embodiments of the process of this invention,
the rare earth salts are combined in aqueous solution with a source of
hydroxide ions. The solution containing the hydrated form of the salt can
then be heated in the manner consistent with deprotonation of the hydrated
form of the salt. The interaction of the hydrated salt and hydroxide ion
result in an accelerated deprotonation of coordinated water molecules
associated with the metal salt. The source of hydroxide ions which is
suitable for use in this process is preferably an organic compound, such
as urea, which undergoes a controlled release of hydroxide ions within the
temperature range conducive to the deprotonation of the hydrated form of
the metal salt.
In the preferred embodiments of this invention, the deprotonation of the
hydrated rare earth cation is effected within a temperature range of from
about 70.degree. to about 90.degree. C. The temperature which is selected
is critical in that is will control not only the kinetics of formation of
a precursor or intermediate species, but also the rate of release of
hydroxide ion.
The pH of the aqueous media is initially adjusted within the range of from
about 4.5 to 6, depending upon the specific rare earth salt from which the
colloidal particles which are to be prepared. Buffering of the solution is
avoided in order to prevent particle aggregation in systems of such high
ionic strength. As the solution ages, the pH will turn decidedly more
acidic. As discussed later in another context, the relative acidity of the
aqueous media can affect the rate of generation of the colloidal particle,
their particle size and particle size distribution.
The kinetics of formation of the precursor or intermediate species is a
critical feature of the process of this invention. The deprotonation of
the hydrated rare earth cations proceeds at a controlled rate at the
temperature and pH specified in this process. The concurrent generation of
hydroxide ions within the reaction mass accelerates this deprotonation
process consistent with the controlled formation of this precursor
species. The objective to this process further require that the
deprotonation of the hydrate rare earth cations results in the formation
of sufficient precursor species to reach critical supersaturation
concentration. At this point, only a single burst of nuclei is formed, and
particle growth thereupon proceeds by diffusion of solutes onto these
existing nuclei. By controlling the kinetics of formation of this
intermediate species, only one burst of nuclei occurs and, thus, particle
size distribution is accordingly controlled. Where, for example, repeated
nucleation is allowed to occur sporadically over a finite interval,
particle size distribution would broaden dramatically. By controlling the
kinetics of formation of the precursor of the nuclei, it is also possible
to produce a stable dispersion of colloidal particle of rare earth salts
having narrow particle size distribution. The process of this invention,
thus, provides a unique pathway for synthesis of a dispersion of colloidal
particles of narrow particle size distribution.
The chemical composition of the colloidal particles was quite predictable.
The salts of gadolinium, terbium, europium and samarium consistently
produced colloidal particles of the corresponding hydroxycarbonate. The
chemical composition of the colloidal particles reflected not only the
processing history, but also the presence of additives in the reaction
medium. Thus, the presence of carbonate in the particle was neither
unexpected, nor inconsistent with the objectives of this process (namely,
the synthesis of the corresponding hydrous oxide). These hydroxycarbonates
were readily convertible to the corresponding oxides by heating these
hydroxycarbonate particles under conditions conducive to thermal
decomposition (i.e. oxidizing atmosphere and temperatures in the range
from about 600.degree. to 850.degree. C.). This conversion did not
otherwise change the essential morphological characteristics or properties
of these colloidal materials.
In certain instances, the colloidal particles prepared in accordance with
this process were essentially spherical in shape and amorphous (i.e.
gadolinium hydroxycaronate). These gadolinium particles are also
fluorescent and are compatible for use with complex biological fluids. For
certain applications, it may be desirable to subject such particles to
calcination at elevated temperature (e.g. 600.degree.-850.degree. C.).
This calcination process resulted in the controlled decomposition of the
hydroxycarbonate to the corresponding oxide and a phase transformation of
the amorphous hydroxycarbonate particles to crystalline oxide particles,
without otherwise alteration of the particles gross morphological
characteristics.
The process of this invention also surprisingly lends itself to a
continuous flow synthesis of colloidal particles from rare earth salts.
The continuous flow approach to such synthesis enables achievement of
anticipated efficiencies over the more traditional batch ("dry")
manufacturing techniques.
The laboratory scale equipment and process flow illustrated in FIG. 6 is
capable of production of from about 1 to 5 grams of colloidal particles
per hour. The feed stream comprising the rare earth salt, acid and organic
base (optional) (in the appropriate relative proportions) is prepared in a
reservoir (2). The reservoir can be a conventional separatory funnel
having an opening on one end (4) thereof for the introduction of
additional feedstock ("make-up" reagents), a valve (6) for metering or
controlling the flow of feedstock from the funnel, and a fitting on the
dispensing tip (8) of the funnel adapted to accept tubing or conduit. This
conduit connects the reservoir to what can be characterized as a buffer
(12). This buffer is simply a convoluted section of conduit of sufficient
length to thermally isolate (i.e. buffer) the feedstock, in the separatory
funnel, from a pre-heater condenser (20). The pre-heater condenser can
typically include an internal heating element or simply be connected to a
source of heated fluid. The residence time of the feedstock in the
pre-heat condenser is controlled both by the cross-section of the conduit
within the condenser and the flow rate. The feedstock, which is withdrawn
from, or exits, the pre-heat condenser, has been heated in the pre-heat
condenser to essentially the same temperature as the reactor column. By
the time the feedstock is withdrawn from the pre-heat condenser, the
formation of precursor (nuclei) of the colloidal particles has been
essentially completed.
The further reaction of the constituents (solute) of feedstock and the
pre-formed nuclei now proceeds to the degree desired in the reactor column
(30). The volume of the reactor column relative to the pre-heat condenser
is maintained at a ratio of about 10:1 to provide adequate "aging" of
reactants and controlled particle growth. The flow, or residence time, of
materials through the reactor is controlled by a pump which draws
materials from a side arm (24) near the base of the reactor. The pump, in
this illustration, is peristaltic in operation. The rate at which the pump
operates is, in turn, controlled by a timer (32).
In a specific embodiment of the continuous flow process of the type
illustrated in FIG. 6, the pre-heat condenser had a capacity of 8 cubic
centimeters and the reactor, a capacity of 80 cubic centimeters. In this
specific embodiment of this process, the residence time of the nuclei in
the reactor was on the order of about 40 minutes or less, depending upon
the size of particle desired. In order to achieve this residence time,
fluid was withdrawn from the side arm near the bottom of the reactor, at a
rate of about 2 cubic centimeters per minute (120 cc/hour). This flow rate
insured a continuous production of 1 to 5 grams of colloidal particles per
hour.
During this accelerated aging process within the reactor, particle growth
continued essentially uninterrupted, with the larger particles forming
progressively, and collecting toward the bottom of the reactor (due to
their relatively longer residence time within the reactor). These
particles did, however, remain in stable suspension and could be readily
withdrawn from the reactor and concentrated by conventional techniques. If
desired, these particles could be dried and stored as powders.
Because of the stability of dispersions of these colloidal particles in
fluid (aqueous) media, it is possible to utilize relatively simple
photo-optical technique for the characterization of a number of their
physical properties (e.g., electrophoretic mobility of particles in fluids
can be used to determine surface charge characteristics, which in turn can
be translated into "zeta" potential for the specific material). In
addition to determination of the suspended particles surface charge,
photo-optical measurements can be used to obtain both particle size and
size distribution; photo responsiveness (i.e. fluorescence); and
refractive index.
EXAMPLES
The following materials and procedures were used in the preparation of the
novel monodispersed particles of this invention. Parts and percentages
appearing is such examples are by weight unless otherwise stipulated.
Equipment and techniques utilized in this process and in the evaluation or
characterization of the colloidal particles derived from this process are
standard (if unspecified) unless stated otherwise.
I. Synthesis Procedures
The preparation of colloidal particles from rare earth salts is
accomplished utilizing standard laboratory equipment and techniques. The
reactants, typically solutes, were initially dissolved in a common solvent
(water) in a common reaction vessel; the pH of the solution adjusted to
the appropriate value; and, the solution thereafter heated in a closed
loop reactor for the desired reaction interval. The reaction temperature
and pH were carefully monitored in order to insure their maintenance
within prescribed limits.
II. Characterization of Physical Properties
The colloidal particles prepared by the process of this invention can be
separated from the fluid media and dried. The structure of these particles
was studied by x-ray diffraction analysis, using a Phillips
diffractometer; particle sizing performed by standard light scattering
polarization-ratio method (particles dispersed in fluid); and by scanning
electron microscopy (dry powders). The surface charge characterization was
determined by electrokinetic measurements on a PenKem 3000 System, and the
chemical surface composition identified by classical chemical analytical
procedures and IR spectroscopy (Perkin-Elmer 1430 recording infrared
spectrophotometer). A Perkin-Elmer LS-5 fluorescence spectrophotometer was
used for fluorescence studies on rare earth colloidal particle
dispersions. Multipoint BET gas absorption techniques (Quantasorb
equipment, having a linear flow controller) were used for determinations
of specific surface area.
EXAMPLE 1
Synthesis of Spherical Colloidal Particles of Gadolinium Hydroxycarbonate
(a) A colloidal dispersion was prepared in accordance with the above
Synthesis Procedures utilizing the following materials and under the
following conditions:
GdCl.sub.3 : 6.times.10.sup.-3 mol dm.sup.-3
Urea: 0.5 mol dm.sup.-3
Initial pH: .about.5
Temperature: 85.degree. C.
The resultant colloidal particles have a modal particles diameter of 0.2
micrometers after 30 minutes of aging and 0.6 micrometers after 120
minutes of aging.
(b) A second colloidal dispersion was prepared in accordance with the above
Synthesis Procedures utilizing the following materials and under the
following conditions:
GdCl.sub.3 : 6.times.10.sup.-3 mol dm.sup.-3
Urea: 0.2 mol dm.sup.-3
pH: 4.6
H.sub.2 SO.sub.4 : 1.times.10.sup.-4 mol dm.sup.-3
Temperature: 85.degree. C.
The resultant colloidal particles have a modal diameter of 0.1 micrometers
after 30 minutes of aging and 0.2 micrometers after 120 minutes of aging.
The effects of increased acidity upon particle size is predictive since
deprotonation of the rare earth hydrate is retarded at lower pH.
The physical properties of the colloidal particles prepared in accordance
with this example were determined in the aforedescribed manner. The
particles thus obtained were confirmed to be amorphous in character and of
a narrow particles size distribution. These particles were fluorescent at
the wave lengths specified in Table I. Calcination of these powders at
temperatures in the range of from about 300.degree. to 850.degree. C.,
resulted in their crystallization, a weight loss of approximately thirty
percent (30%), conversion to the corresponding (hydrous) oxide, and an
increase in porosity. The surface area, however, remained essentially the
same (3 m.sup.2 /gram), nor was there any change in the specific surface
area. The particles remained redispersible in aqueous media. The
refractive index of these particles (at 546 and 436 nm) was approximately
1.8.
EXAMPLE 2
Synthesis of Terbium Hydroxycarbonate
(a) A colloidal dispersion was prepared in accordance with the above
Synthesis Procedures utilizing the following materials and under the
following conditions:
TbCl.sub.3 : 6.times.10.sup.-3 mol dm.sup.-3
Urea: 4.times.10.sup.-1 mol dm.sup.-3
Initial pH: .about.5.5
Temperature: 85.degree. C.
Aging Time: 1 hour
Particle Size (modal diameter): 0.25 micrometers
EXAMPLE 3
Synthesis of Europium Hydroxycarbonate
(a) A colloidal dispersion was prepared in accordance with the above
Synthesis Procedures utilizing the following materials and under the
following conditions:
EuCl.sub.3 : 6.times.10.sup.-3 mol dm.sup.-3
Urea: 1.6 mol dm.sup.-3
Initial pH: 5.3
Temperature: 85.degree. C.
Aging Time: 1 hour
Particle Size: 0.15 micrometers
The colloidal particles produced under theses conditions had a modal
diameter of 0.2 micrometers and the standard deviation, 0.05 micrometers.
EXAMPLE 4
Synthesis of Samarium Hydroxycarbonate
(a) A colloidal dispersion was prepared in accordance with the above
Synthesis Procedures utilizing the following materials and under the
following conditions:
Sm(NO.sub.3).sub.3 : 6.times.10.sup.-3 mol dm.sup.-3
Urea: 0.5.times.10.sup.-1 mol dm.sup.-3
pH: .about.5.5
Temperature: 85.degree. C.
Aging Time: 1 hour
Particle Size (modal diameter): 0.25 micrometers
TABLE I
The fluorescence emission spectra of samples of gadolinium (III), europium
(III), and terbium (III) hydroxycarbonates were measured with a
Perkin-Elmer LS-5 fluorescence spectrophotometer. Enhanced emission
spectra of the samples in aqueous solutions were observed as the
excitation wavelength (e.w.) is smaller than 546 nm. The spectra of the
different samples are similar to each other at excitation wavelengths
other than 230 nm. The results are tabulated as follows:
______________________________________
e.w./nm Emission Spectra/nm
______________________________________
230 330-410, 500 (s.p.) 550 (only for Tb)
265 291 (s.p.), 580 (s.p.)
290 321 (s.p.), 330-400, 643 (s.p.)
360 410 (s.p.)
394 454 (s.p.), 591 (s.p.)
436 470 (s.p.), 512 (s.p.), 654 (s.p.)
488 510 (s.p.), 531 (s.p.), 733 (s.p.)
546 590-605
590 610-620 (weak band)
633 650-660 (weak band)
______________________________________
s.p. = sharp peak
EXAMPLE 5
One milliliter of a 10% (w/w) aqueous suspension of gadolinium oxide is
initially washed with methanol (.times.3). The oxide is once again washed
with methylene chloride (.times.3) and thereafter contaced (.times.3) with
a series of methylene chloride solutions containing 1% polystyrene (w/v),
thereby imparting a polymer coating (deposit) upon the particle's surface.
The coated particles are washed once again with alternating solutions of
methanol and water in a sonicator. The particles are separated from the
final wash fluid by centrifugation and resuspended in sufficient volume of
a phosphate buffered saline to form a 10% (w/v) suspension. Monoclonal
antibody specific for a T-cell surface (lymphocyte phenotype) marker are
adsorbed onto the polystyrene coated gadolinium oxide particles by simply
contacting said particles and antibody in the buffered saline solution.
The concentrations of antibody added to the particle suspension is
approximately 1 mg/ml. The antibody coated particles are now mixed with a
solution of bovine serum albumin (1 mg/ml) to block non-specific binding
sites on the particles. The antibody coated particles prepared in the
above manner are now ready for use or can be stored under refrigeration
for use at a later time.
EXAMPLE 6
An aliquot of a fluid suspension of antibody coated gadolinium oxide
particles (prepared in accordance with Example 5) is combined with a
highly diluted sample of whole blood (the extent of dilution being
dictated by the analytical protocol of the analytical instrument). The
colloidal particles and sample are swirled to insure essentially uniform
distribution of the materials of the resultant dispersion. After a
relatively brief interval (<15 seconds), the dispersion is transferred to
a sample containers and the container inserted into an EPICS Model C Flow
Cytometer (available from the Epics Division of Coulter Corporation,
Hialeah, Fla.). The sample is processed in accordance with standard flow
cytometer photo-optical principles. Sample excitation is achieved with
ultraviolet light (excitation at 365 nm). The scattergram produced by such
analysis permits ready identification and differentiation of the subset of
cells of the lymphocyte population which had been tagged with the
flourescent gadolinium oxide particles.
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